Medical devices intended for implant into the body or bodily tissues of a mammal (including a human), as for example medical prostheses or surgical implants, may be fabricated from a variety of materials including various metals, metal alloys, plastic or polymer materials, solid resin materials, glassy materials and other materials including various biodegradable materials as may be suitable for the application and appropriately biocompatible. As examples, certain stainless steel alloys and cobalt-chrome alloys have been used. Such devices include for example, without limitation, vascular stents and artificial joint prostheses, etc. It has often been found beneficial to coat the surfaces of such devices with a therapeutic agent such as a medicine or drug to increase the likelihood of a successful outcome for the surgical implant treatment.
For example, in the case of an implantable vascular stent, it is often desirable to apply drugs to the surface of the stent prior to its introduction into a vascular vessel. Implantable vascular stents may be fabricated from metal materials or may be fabricated from biodegradable materials. In the past, it has been the experience that therapeutic drugs, when applied directly to an expandable vascular stent, are not as effective as intended. Sometimes, the therapeutic agent is released (elutes) from the surface too rapidly (perhaps even washing off almost entirely during implantation of the stent. Other times the stent-drug combination does not withstand the mechanical stresses imposed during compression, expansion, or flexing of the stent required before and during implantation and the drug coat cracks, flakes, or delaminates during mechanical deformation—this generally results in either loss of the drug, or an undesirable change in the rate at which it elutes, following implantation. Especially when larger drug loads requiring thicker coatings are indicated, the problem of retaining an undamaged drug coating on the stent during and following mechanical strains has been problematical. It has become a common practice to use a polymer matrix to bond the therapeutic agent to such stents or to encapsulate the drug both to improve the durability and ductility of the coating and to help control the in-situ drug elution rate. It is now believed that such polymers have undesirable side effects that can result in unfavorable outcomes. There is a need for a drug-coated expandable vascular stent that doesn't employ a polymer or other binder matrix to control mechanical and elution properties, but where a robust and durable drug coating is applied directly on the bare stent in a manner that provides a suitable elution rate and which withstands the normal mechanical activities necessary to implant the stent without shedding or unacceptably compromising the coating.
Many methods are known for coating surgical implants with drugs or drug-polymer matrices. Among these, dipping and spray applications have been commonly used and various spray techniques have been employed. Usual spray techniques have involved dissolving one or more therapeutic agents and perhaps including a polymer matrix material in a solvent to form a solution with suitable properties for spray application. WIPO patent application publication WO06086693A2 published Aug. 17, 2006 (Brown) describes an apparatus for vacuum spraying medical devices with a drug-polymer coating using an ultrasonic nozzle. In U.S. Pat. No. 7,198,675 granted Apr. 3, 2007 Fox et al. describe mounting a bare stent on a mandrel fixture and spray-coating selective surfaces of the stent by spraying a solvent, drug, polymer, or combination of any of solvent, drug, and polymer. Still, the clinical problem remains that vascular stents coated with drug alone have not performed well and drug-polymer combinations have introduced undesired side effects.
When many drugs are coated onto expandable stents, it is seen that a single application cannot apply the necessary drug load needed for the desired therapy to be effective. With thick coatings, there are difficulties in removing the solvent without undesirable effects. By using multiple layer coatings, greater drug loads can be applied to a stent as taught in U.S. Pat. No. 5,464,650 granted Nov. 7, 1995 to Berg et al. but such multi-layer coatings have been most successful with drug-polymer matrix coatings. Compared to multi-layer drug-polymer matrix coatings, the multi-layer drug-only coatings, being thicker, are more brittle and have less strength and so have tended to crack and delaminate more severely when the stents are flexed, expanded or subjected to other mechanical strains.
Gas cluster ion beams (GCIB) are known, and have been used to process surfaces for purposes of cleaning, etching, smoothing, film growth, and the like. Gas cluster ions are ionized, loosely bound, aggregates of materials that are normally gaseous under conditions of standard temperature and pressure—typically consisting of from a few hundreds atoms or molecules to as many as a few ten thousands of atoms or molecules. Gas cluster ions can be accelerated by electric fields to considerable energies of thousands of keV. However because of the large number of atoms or molecules in each gas cluster ion, and because of the loose binding, their effect upon striking a surface is very shallow—the cluster is disrupted at impact and each atom or molecule carries only a few eV of energy. At the surface, instantaneous temperatures and pressures can be very high at gas cluster ion impact sites, and a variety of surface chemistry, etching, and cleaning effects can occur. Gas cluster ion beams have been used to clean and smooth medical implants and to adhere drugs to the surfaces of medical devices including stents (See U.S. Pat. No. 7,105,199 granted Sep. 12, 2006 to Blinn et al. and U.S. Pat. No. 6,676,989, granted Jan. 13, 2004 to Kirkpatrick et al.)
It is therefore an object of this invention to provide methods and systems for coating medical devices such as expandable vascular stents with drugs without the necessity of a polymer coat or matrix to promote durability and to control elution rate.
It is a further object of this invention to provide methods and systems for forming multi-layer drug coatings for medical devices that are durable, have controlled drug elution rates, and are well adhered.
A still further object of this invention to provide methods and systems for controlling the elution rate of a drug coating on a medical device by irradiation of the drug coating.
Another object of this invention to provide a drug-eluting medical device, as for example an expandable vascular stent that is polymer-free and, which has a drug coating having a controlled dose as a durable coating or durable multi-layer coating.
An additional object of this invention is to provide a drug-eluting medical device with controlled elution rate and to provide methods and systems for controlling an elution rate of a drug coating on a medical device by incorporating an elution-retarding material within the drug coating and irradiating the drug coating with the incorporated elution-retarding material.